Usami N, Kobayashi K, Furusawa Y, Frohlich H, Lacombe S, Sech C Le
Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization, Oho, Tsukuba, Ibaraki, Japan.
Int J Radiat Biol. 2007 Sep;83(9):569-76. doi: 10.1080/09553000701447130.
In order to study the role of the Linear Energy Transfer (LET) of fast atomic ions in platinum-DNA complexes inducing breaks, DNA Plasmids were irradiated by C(6+) and Fe(26+) ions.
DNA Plasmids (pBR322) loaded with different amounts of platinum contained in a terpyridine-platinum molecule (PtTC) were irradiated by C(6+) ions and Fe(26+) ions. The LET values ranged between 13.4 keV/microm and 550 keV/microm. In some experiments, dimethyl sulfoxide (DMSO) was added.
In all experiments, a significant increase in DNA strand breaks was observed when platinum was present. The yield of breaks induced per Gray decreased when the LET increased. The yield of single and double strand breaks per plasmid per track increased with the LET, indicating that the number of DNA breaks per Gray was related to the number of tracks through the medium.
These findings show that more DNA breaks are induced by atomic ions when platinum is present. This effect increases for low LET heavy atoms. As DSB induction may induce cell death, these results could open new perspectives with the association of hadrontherapy and chemotherapy. Thus the therapeutic index might be improved by loading the tumour with platinum salts.
为了研究快速重离子的传能线密度（LET）在铂 - DNA复合物诱导断裂中所起的作用，用碳（C(6+)）离子和铁（Fe(26+)）离子辐照DNA质粒。
用含不同量三联吡啶 - 铂分子（PtTC）的DNA质粒（pBR322）分别接受碳（C(6+)）离子和铁（Fe(26+)）离子辐照。LET值范围在13.4 keV/μm至550 keV/μm之间。在一些实验中添加了二甲基亚砜（DMSO）。
在所有实验中，当存在铂时，观察到DNA链断裂显著增加。每格雷诱导的断裂产额随LET增加而降低。每条径迹上每个质粒的单链和双链断裂产额随LET增加，这表明每格雷的DNA断裂数与穿过介质的径迹数有关。
这些发现表明，当存在铂时，重离子会诱导更多的DNA断裂。对于低LET重原子，这种效应会增强。由于双链断裂的诱导可能导致细胞死亡，这些结果可能为强子治疗与化疗联合应用开辟新的前景。因此，通过给肿瘤加载铂盐可能会提高治疗指数。
